The impact of the COVID-19 outbreak on emergency general surgery in the first German "hotspot region" Aachen-Heinsberg-A multicentre retrospective cohort study.

This study aimed to observe the impact of the COVID-19 outbreak on acute general surgery in the first German "hotspot" regions of Heinsberg and Aachen, during the first months of the pandemic. The incidence and severity of acute appendicitis, acute cholecystitis and mechanical bowel obstruction, were compared between March and May 2020 and a control period (same months of the previous three years). Pre-, intra- and postoperative data was compared between three regional hospitals of Heinsberg and the closest maximum care, university hospital. A total of 592 operated patients were included, 141 belonging to the pandemic cohort and 451 to the historic cohort. The pandemic group showed higher rates of clinical peritonitis (38% vs. 27%, p = 0.015), higher rates of mean white blood cell count (13.2±4.4 /nl vs. 12.3±4.7 /nl, p = 0.044) and mean C-reactive protein (60.3±81.1 mg/l vs. 44.4±72.6 mg/l, p = 0.015) preoperatively. Specifically in patients with acute appendicitis, there were less patients with catarrhal appendicitis (23% vs. 35%, p = 0.021) and a tendency towards more advanced histological findings in the pandemic cohort. In the university hospital, a 42% reduction in acute operated cases was observed at the onset of the pandemic (n = 30 in 2020 vs. n = 52 in 2019), whereas in the peripheral hospitals of Heinsberg there was only a 10% reduction (n = 111 in 2020 vs. n = 123 in 2019). The onset of the COVID-19 pandemic in our region was accompanied by advanced preoperative and intraoperative findings in patients undergoing emergency general surgery. A greater reduction in acute operated surgical cases was observed at the university hospital, in contrast to the smaller hospitals of Heinsberg, suggesting a possible shift of emergency patients, requiring immediate operation, from maximum care hospital to the periphery.

Mesh biocompatibility: effects of cellular inflammation and tissue remodelling.

Mesh biocompatibility is basically determined by the foreign body reaction (FBR). In contrast to physiological wound healing and scar formation, the FBR at the host-tissue/biomaterial interface is present for the lifetime of the medical device. The cellular interactions at the mesh/tissue interface proceed over time ending up in a chronic inflammatory process. The time course of the FBR has been studied extensively and consists of three crucial steps that are protein absorption, cell recruitment and, finally, fibrotic encapsulation and extracellular matrix formation. Each of these steps involves a complex cascade of immune modulators including soluble mediators and various cell types. Recent research has focused on the cellular and molecular interactions of the distinct phases of the FBR offering a new basis for therapeutical strategies. The highly dynamic process of the FBR is considerably influenced by the biomaterial composition. Modifications of the type of polymer, the material weight, the filament structure and the pore size are realized and have substantial effects on the in vivo biocompatibility. Moreover, modern mesh technology aims to utilize the available implants as carrier systems for bioactive drugs. Studies in animal models account for the efficiency of these drugs that aim to reduce mesh-related infections or to minimize FBR by influencing inflammation or extracellular matrix remodelling. A thorough understanding of the molecular mechanisms of FBR provides a sophisticated background for the development of new biomaterials at least as carrier systems for bioactive reagents to reduce inflammation and to improve clinical outcome.

Damage to the spermatic cord by the Lichtenstein and TAPP procedures in a pig model.

BACKGROUND: Mesh implantation is regarded as the standard treatment of inguinal hernias. Obstructive azoospermia induced by mesh implantation is a rare but serious complication. Whether different operative techniques or mesh materials used have an effect on the integrity of the testicle and spermatic cord remains unclear. MATERIALS: In 12 minipigs a bilateral inguinal hernia repair, either open or laparoscopic, was performed using a standard small-pore polypropylene (PP) or large-pore polyvinyliden fluoride (PVDF) mesh. Next to measurement of the testicular size, thermography of the groin and testicle as a parameter for perfusion was performed preoperatively and at a follow-up at 6 months. Obstructions of the vas deferens were estimated radiographically. Testicular function (Johnson score) and mesh integration (granuloma size, apoptotic cells) were analyzed histologically. RESULTS: Mean testicular size did not change significantly in follow-up compared to preoperative values. Technique and mesh material used failed to have a significant influence. Thermography of the groin following the Lichtenstein technique had significantly higher values at follow-up regardless of the mesh used. This could not been shown for laparoscopic treatment. Thermographic measurements at the testicle showed a significantly increased temperature in all groups compared to preoperative measurements. Only the Lichtenstein PP group showed significantly decreased values in testicular function. Quantity and quality of obstructions seen at vasography were most detectable in the Lichtenstein PP group. There was significantly decreased granuloma formation following PVDF mesh implantation compared to the PP mesh group regardless of the technique used. CONCLUSIONS: Both the technique and the mesh material have an impact on integrity of spermatic cord and testicular function. According to the results of this study, the laparoscopic TAPP procedure using a large-pore PVDF mesh has the least effect compared to preoperative values.

Impact of proinflammatory cytokine knockout on mesh integration.

Placement of mesh is involved in 75-80% of hernia operations. It is known that an exaggerated foreign body reaction leads to clinical complications. To further improve patients outcome using biotechnological agents targeted against tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6), a study was conducted investigating the impact of cytokine knockout on mesh integration. Sixty mice were used: C57BL/6 wild type control, C57BL/6-IL-6 interleukin-6 knockout, C57BL/6-Tnfrsf1a knockout of TNF-alpha receptor 1, and C57BL/6-Tnfrsf1b knockout of TNF-alpha receptor 2. Standard polypropylene mesh was implanted subcutaneously for 7, 21, and 90 days. The inflammatory and connective tissue formation was characterized by diameter of inner cellular infiltrate and outer fibrous capsule of the foreign body granuloma, and by quantity (collagen/protein ratio) and quality (collagen type I/III ratio) of collagen formation. Microscopic investigation of the mesh/host-tissue interface showed typical formation of foreign body granulomas. Ninety days after implantation none of the knockout strains showed significant differences compared to the control group investigating amount of inflammatory and connective tissue formation. Analyzing the quantity of filamentary collagen deposition the C57BL/6-IL-6 group showed significant lowered values compared to the control group 90 days after implantation. In all groups collagen type I/III ratio increased over time as an indicator for maturation of the surrounding collagen formation. However, no difference was found comparing strains at the end of the observation period. The results support the notion that wound healing is affected by cytokine deficiency. However, a desirable reduced amount of inflammatory tissue formation as well as an increased collagen type I/III ratio due to cytokine knockout could not be observed.

Adhesion formation of a polyvinylidenfluoride/polypropylene mesh for intra-abdominal placement in a rodent animal model.

BACKGROUND: Effective laparoscopic ventral herniorrhaphy mandates the use of an intraperitoneal mesh. Visceral adhesions and shrinkage of prosthetics may complicate repairs. The aim of this study was to compare adhesion formation, mesh shrinkage and tissue ingrowth after intra-abdominal placement of a novel two-component monofilament mesh structure made of polypropylene (PP) and polyvinylidenfluoride (PVDF) with current alternatives. MATERIALS AND METHODS: Forty Sprague-Dawley rats were used in this study. Mesh samples were fixed as intra-abdominal only mesh at the right lateral abdominal wall. The study groups were: PVDF+PP (polypropylene parietally and polyvinylidenfluoride viscerally), PP+Col (polypropylene with a collagenoxidized film), ePTFE (smooth surface viscerally and a textured surface parietally), and PP (a pure polypropylene mesh serving as control). The meshes were explanted after 30 days. Adhesions were scored as a percentage of explanted biomaterials' affected surface area; prosthetic shrinkage was calculated. Foreign-body reaction to mesh materials was measured by investigating the amount of inflammatory infiltrate and fibrotic tissue formation. RESULTS: In terms of adhesion score, the pure PP mesh showed the highest values followed by the ePTFE, PVDF+PP, and PP+Col meshes. Quantitative assessment of adhesion area revealed a significantly higher value of the pure PP mesh sample (62.0 +/- 22.1%) compared with the PP+Col (26.8 +/- 12.1%) and the PVDF+PP mesh (34.6 +/- 8.2%). Percentage of shrinkage showed a significantly higher value of the ePTFE mesh (52.4 +/- 13.9%) compared with all other mesh modifications (PP+Col 19.8 +/- 13.9%, PVDF+PP 19.9 +/- 7.0%, and PP 26.8 +/- 9.5%). Inflammatory infiltrate was significantly reduced in the PVDF+PP mesh group compared with all other mesh samples. CONCLUSION: The use of the novel two-component monofilament mesh structure made of polypropylene and polyvinylidenfluoride was found to be favorable regarding adhesion formation and mesh shrinkage compared to conventional mesh materials used for intra-abdominal placement.

Different tissue reaction of oesophagus and diaphragm after mesh hiatoplasty. Results of an animal study.

BACKGROUND: Laparoscopic mesh-reinforcement of the hiatal region in the treatment of gastroesophageal reflux disease (GERD) and paraesophageal hernia (PEH) reduces the risk of recurrence. However, there are still controversies about the technique of mesh placement, shape, structure and material. We therefore compared tissue integration and scar formation after implantation of two different polypropylene-meshes in a rabbit model. METHODS: A total of 20 female chinchilla rabbits were included in this study. Two different meshes (Polypropylene PP, Polyglecaprone 25 Composite PP-PG) were implanted on the abdominal diaphragm around the oesophagus. After 3 months the implanted meshes were excised en-bloc. Histological and morphological analyses were carried out accordingly proliferation rate, apoptosis and collagen type I/III ratio. RESULTS: Regarding proliferation rate of oesophagus PP (9.31 +/- 3.4%) and PP-PG (13.26 +/- 2.54%) differ in a significant (p = 0.0097) way. In the diaphragm we found a significant (p = 0.00066) difference between PP (9.43 +/- 1.45%) and PP-PG (18.73 +/- 5.92%) respectively. Comparing oesophagus and diaphragm we could prove a significant difference within PP-PG-group (p = 0.0195). Within PP-group the difference reached no statistical significance (p = 0.88). We found analogous results regarding apoptosis.Furthermore, there is a significant (p = 0.00013) difference of collagen type I/III ratio in PP-PG (12.28 +/- 0.8) compared to PP (8.44 +/- 1,63) in case of oesophageal tissue. Concerning diaphragm we found a significant difference (p = 0.000099) between PP-PG (8.85 +/- 0.81) and PP (6.32 +/- 1.07) as well. CONCLUSION: The histologic and morphologic characteristics after prosthetic enforcement of the hiatus in this animal model show a more distinct tissue integration using PP-PG compared to PP. Additionally, different wound healing and remodelling capability influence tissue integration of the mesh in diaphragm and oesophagus.

Biomechanical analyses of overlap and mesh dislocation in an incisional hernia model in vitro.

BACKGROUND: Incisional hernia repair is one of the most common surgical complications. Despite the introduction of mesh techniques of repair, recurrences are still prevalent. The aim of the current study was to evaluate the dependence of mesh dislocation on defect size, facial overlap, mesh-position, and orientation of the mesh in cases of anisotropic stretchability. METHODS: An in vitro incisional hernia model was used, which consisted of a pressure chamber, an elastic silicone pad representing the peritoneal sac, and a silicone mat with bovine muscle tissue representing the abdominal wall. Intrinsic pressure (up to 200 mm Hg) was generated within the pressure chamber by continuous inflation with CO(2). A slit-like or flap-like defect was created in the silicone mat to simulate small or large hernia defects, respectively. The implanted mesh was arranged in both onlay and sublay configurations. A large pore polypropylene mesh with significant anisotropic stretchability was investigated, whereas overlaps of 2, 3, and 4 cm were applied. RESULTS: Despite the application of pressures up to 200 mm Hg, no mesh ruptures occurred. In the slit-like defect model, the minimal overlap required to prevent dislocation at 200 mm Hg was 3 cm using the sublay technique provided that the mesh was positioned with its most stretchable axis parallel to the largest slit dehiscence. Perpendicular rotation of the mesh resulted in dislocation at 160 mm Hg, despite using an overlap of 3 cm. Mesh reinforcement showed less stability in both the onlay position and the flap-like defect. CONCLUSION: An overlap of 3 cm is sufficient to prevent early mesh dislocation. Meshes with anisotropic stretchability should be orientated with the most stretchable axis in the direction of least overlap.

Regulation of MMP-2 gene transcription in dermal wounds.

Matrix metalloproteinase-2 (MMP-2, gelatinase A) plays an essential role in angiogenesis, inflammation, and fibrosis. These processes are critical for wound healing and accordingly elevated levels of MMP-2 expression have been detected after skin injury. Our goal was to investigate the transcriptional activation of the MMP-2 gene in a model of skin injury by using two different MMP-2/LacZ-reporter mice. Upon skin injury MMP-2 expression was upregulated, whereas tissue from normal skin stained negative except for occasional macrophages, sweat glands, and hair follicles. Skin injury also activated MMP-2 proteolytic activity and reporter gene expression. We demonstrate that MMP-2 regulatory sequences -1686/+423 drive appropriate injury-induced MMP-2-promoter activation. Reporter gene expression was predominantly detectable in endothelial cells and in macrophages. Deletion of the 5' responsive element, denoted RE-1, residing at -1241/+423 bp of the regulatory sequence led to abrogated MMP-2 transcription in vivo. The findings define a crucial role for the enhancer element RE-1 in injury-induced MMP-2 transcription of the skin.

Polymeric meshes induce zonal regulation of matrix metalloproteinase-2 gene expression by macrophages and fibroblasts.

Matrix metalloproteinase-2 (MMP-2) is a key regulator in wound healing that orchestrates tissue remodeling. In the present study the spatial and temporal distribution of MMP-2 gene transcription, protein synthesis, and enzymatic activity were analyzed following polymeric mesh (polyglactin, polypropylene) implantation in transgenic reporter mice harboring MMP-2 regulatory sequences -1686/+423 or -1241/+423. Polymers induced MMP-2 promoter activity in macrophages within the foreign body granuloma via sequences -1686/+423 with concomitantly up-regulated protein synthesis and enzymatic activity. Macrophages distant from mesh filaments exhibited low MMP-2 expression levels. Fibroblasts surrounding mesh material displayed strong MMP-2 gene transcription independent of the included promoter sequences, whereas fibroblasts without close contact to mesh material had low MMP-2 synthesis rates due to silencing activity of sequences -1686/-1241. In vitro studies support a cellular crosstalk concept, as macrophages trans-repressed MMP-2 gene transcription in fibroblasts. The zonal and cell-specific regulation of MMP-2 gene transcription illuminates an intimate cellular crosstalk in foreign body reaction that may provide a new approach for mesh modification.

Improved collagen type I/III ratio at the interface of gentamicin-supplemented polyvinylidenfluoride mesh materials.

BACKGROUND: Formation of recurrent inguinal and incisional hernia shows an underlying defect in the wound-healing process with an insufficient quality of scar formation. Even after mesh repair an altered collagen formation and insufficient mesh integration has been found as main reason for recurrences. Therefore, the development of bioactive mesh materials to achieve a local modification of the scar formation to improve patients outcome is advisable. MATERIALS AND METHODS: A polyvinylidenfluoride mesh material (PVDF) was constructed and surface modified by plasma-induced graft polymerization of acrylic acid (PVDF + PAAc). Surface supplementation was sought by binding of gentamicin to the provided active sites of the grafted mesh surfaces (PVDF+PAAc+Gentamicin). In vivo modulation of collagen formation was evaluated in a standardized animal model where an abdominal wall replacement was performed in 45 Sprague-Dawley rats. Seven, 21, and 90 days after mesh implantation, collagen/protein ratio and the collagen type I/III ratio as well as the expression of type I alpha 1 collagen mRNA (SYBR Green real-time RT-PCR) were analyzed at the perifilamentary region. Additionally, expression of matrix metalloproteinases (MMP-8/-13) has been investigated immunohistochemically. RESULTS: Implantation of the PVDF + PAAc + Gentamicin mesh induced a significantly decreased expression of MMP-8 and MMP-13 at the interface 21 and 90 days after implantation compared to the other groups. Whereas no significant effect was observed comparing the overall collagen/protein ratio, the quality of collagen formation expressed by the collagen type I/III ratio showed significantly higher ratios around the PVDF + PAAc + Gentamicin mesh 21 and 90 days after implantation. Correspondingly, an up to 5.3-fold expression of type I alpha 1 collagen mRNA was found. CONCLUSION: The present data confirm that a surface modification of PVDF mesh samples using plasma-induced graft polymerization of acrylic acid and supplementation of gentamicin is able to improve scar quality and mesh integration.

Hernia fibroblasts lack beta-estradiol-induced alterations of collagen gene expression.

BACKGROUND: Estrogens are reported to increase type I and type III collagen deposition and to regulate Metalloproteinase 2 (MMP-2) expression. These proteins are reported to be dysregulated in incisional hernia formation resulting in a significantly decreased type I to III ratio. We aimed to evaluate the beta-estradiol mediated regulation of type I and type III collagen genes as well as MMP-2 gene expression in fibroblasts derived from patients with or without history of recurrent incisional hernia disease. We compared primary fibroblast cultures from male/female subjects without/without incisional hernia disease. RESULTS: Incisional hernia fibroblasts (IHFs) revealed a decreased type I/III collagen mRNA ratio. Whereas fibroblasts from healthy female donors responded to beta-estradiol, type I and type III gene transcription is not affected in fibroblasts from males or affected females. Furthermore beta-estradiol had no influence on the impaired type I to III collagen ratio in fibroblasts from recurrent hernia patients. CONCLUSION: Our results suggest that beta-estradiol does not restore the imbaired balance of type I/III collagen in incisional hernia fibroblasts. Furthermore, the individual was identified as an independent factor for the beta-estradiol induced alterations of collagen gene expression. The observation of gender specific beta-estradiol-dependent changes of collagen gene expression in vitro is of significance for future studies of cellular response.

Light weight meshes in incisional hernia repair.

Incisional hernias remain one of the most common surgical complications with a long-term incidence of 10-20%. Increasing evidence of impaired wound healing in these patients supports routine use of an open prefascial, retromuscular mesh repair. Basic pathophysiologic principles dictate that for a successful long-term outcome and prevention of recurrence, a wide overlap underneath healthy tissue is required. Particularly in the neighborhood of osseous structures, only retromuscular placement allows sufficient subduction of the mesh by healthy tissue of at least 5 cm in all directions. Preparation must take into account the special anatomic features of the abdominal wall, especially in the area of the Linea alba and Linea semilunaris. Polypropylene is the material widely used for open mesh repair. New developments have led to low-weight, large-pore polypropylene prostheses, which are adjusted to the physiological requirements of the abdominal wall and permit proper tissue integration. These meshes provide the possibility of forming a scar net instead of a stiff scar plate and therefore help to avoid former known mesh complications.

Hernia recurrence as a problem of biology and collagen.

Usually an abdominal wall hernia is regarded as a mechanical problem with a local defect which has to be closed by technical means. Despite the introduction of several therapeutic improvements, recurrent hernias still appear in 10-15%. Therefore, reasons for a recurrence are discussed in a more fundamental way. It is assumed that a failure mainly depends on the quality of the repair. Correspondingly, in principle, the close causal relationship between the technical component and its failure during time is reflected by an s-shaped outcome curve. In contrast, the configuration of the outcome curve changes markedly if a breakdown is caused by numerous components. Then, the superposition of all incidence curves inevitably leads to a linear decline of the outcome curve without any s-shaped deformation. Regarding outcome curves after hernia repair, the cumulative incidences for recurrences of both incisional and inguinal hernia show a linear rise over years. Considering the configuration of outcome curves of patients with hernia disease, it may therefore be insufficient to explain a recurrence just by a failing technical repair. Rather, biological reasons should be suspected, such as a defective wound healing with impaired scarring process. Recent molecular-biological findings provide increasing evidence of underlying biochemical alterations in patients with recurrent hernia. Until predicting markers to identify patients with an impaired wound healing are available and considering the formation of insufficient scar as the underlying disease, the consequences for every surgical repair should be a supplementary reinforcement with nonabsorbable alloplastic nets as flat meshes with an extensive overlap.

Gentamicin supplementation of polyvinylidenfluoride mesh materials for infection prophylaxis.

Hernia repair evolved from pure tissue repair to mesh repair due to decreased recurrence rates. However, concern exists about mesh-related infections occurring even several years after initial operation. Therefore, a polyvinylidenfluoride (PVDF) mesh material was constructed and surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Antimicrobial treatment was sought by binding of gentamicin (PVDF+PAAc+Gentamicin). In vitro efficacy and cytotoxicity was measured by agar diffusion test, L929 cytotoxicity testing and by analyzing the amount of gentamicin release from the mesh surface. In vivo biocompatibility was evaluated in 45 Sprague-Dawley rats. 7, 21 and 90 days after mesh implantation the amount of inflammatory and connective tissue as well as the percentage of proliferating (Ki67) and apoptotic cells (TUNEL) were analyzed at the perifilamentary region. Agar diffusion tests showed sufficient local antimicrobiotic effects against the bacteria tested after 24h of incubation. No signs of cytotoxicity could be identified by L929 testing. Furthermore, surface modification did not affect the in vivo biocompatibility. At the end of the observation period, no significant differences were found for the perifilamentary amount of inflammatory cells and connective tissue and the percentage of Ki67 and TUNEL positive stained cells. The presented data confirm that an antibiotic surface modification of PVDF mesh samples is feasible. By analyzing cytotoxicity in vitro as well as biocompatibility in vivo no side effects were observed.

Impact of pressure and gas type on anastomotic wound healing in rats.

BACKGROUND: Laparoscopic techniques in the treatment of various bowel diseases have become more and more popular in today's clinical routine. However, knowledge about the impact of a carbon dioxide (CO(2)) pneumoperitoneum on the quality of healing of the intra-abdominal wound is rare. We therefore investigated the effects of pressure and gas type on anastomosis healing in a rat model. METHODS: Laparotomy and twofold ileo-ileal anastomosis was performed in 78 male Sprague Dawley rats. A CO(2) or a helium pneumoperitoneum of 3 mmHg (each, n=18) or of 6 mmHg (each, n=12) was maintained before and after ileo-ileostomy. Rats in the control group ( n=18) received no pneumoperitoneum. Animals were killed after 5 and 10 days. As indicator of bowel function, mean body weights were compared between the groups. One region of the anastomosis was subjected to computerised bursting-pressure measurements, while the second was explanted for subsequent histopathological examinations: collagen synthesis and degradation was determined by the ratio of collagen type I to type III and by the matrix metalloproteinase MMP-13. The extent of new mucosal layer formation was measured in haematoxylin and eosin (H and E)-stained sections. RESULTS: Alteration in mean body weight and the mean anastomosis bursting pressures did not differ between the groups. Likewise, histological examination revealed no statistically significant differences, either in the values for collagen I/III ratios or in the extent of mucosal proliferation. After 10 days, 6 mmHg helium pneumoperitoneum was associated with a more pronounced expression of MMP-13 than that of controls. CONCLUSIONS: A CO(2) pneumoperitoneum with pressures of 3 mmHg and 6 mmHg was found to have no significant impact upon the healing of anastomosis wounds in rats. Helium pneumoperitoneum offers no advantages over CO(2).

Decreased collagen type I/III ratio in patients with recurring hernia after implantation of alloplastic prostheses.

BACKGROUND: Abnormal collagen metabolism is suspected to play an important role in the pathogenesis of recurring inguinal and incisional hernias. Whereas alloplastic prostheses are nowadays routinely used, the quantity and quality of collagen formation after repair in humans has not been analysed in a large cohort. METHOD: Seventy-eight prostheses (Prolene, Atrium, Marlex, Vypro, Mersilene, Gore-Tex) implanted for inguinal and incisional hernia repair were explanted because of recurrence, chronic pain or infection. The mean implantation period was 17.9+/-11.2 (range 0.5-48) months. Collagen formation was investigated quantitatively (collagen-protein ratio) and qualitatively (collagen type I/III ratio). Results were related to clinical data that included gender, age, implantation period, indication for implantation/explantation, type and location of prosthesis. RESULTS: Mean collagen-protein ratio was 45.3+/-8.5 microg/mg, with significant differences between male (43.8+/-9.1 microg/mg) and female tissue samples (48.1+/-6.8 microg/mg, P=0.033). The mean collagen type I/III ratio of all samples investigated was 2.1+/-1.4. Samples explanted for recurring hernias exhibited a significantly decreased ratio (1.3+/-0.7, P<0.05) compared to samples explanted because of pain (3.4+/-1.2) or infection (2.9+/-1.6). Multivariate analysis excluded independent effects of age, gender, indication for implantation of prostheses, location and implantation period on collagen type I/III ratio. CONCLUSION: The present study confirms the importance of a biological approach, next to technical aspects, to the understanding of the pathogenesis of recurrent hernia formation and underscores the presence of a disturbed scarring process. The composition of scar tissue with a lowered collagen type I/III ratio and, therefore, reduced tensile strength may be a major contribution to hernia recurrence.

Effect of tension induced by Shouldice repair on postoperative course and long-term outcome.

OBJECTIVE: To record intraoperative tension during Shouldice hernioplasty and correlate it with postoperative course and long-term outcome. DESIGN: Prospective clinical trial. SETTING: University clinic, Germany. SUBJECTS: 20 male patients undergoing elective primary inguinal hernia repair by Shouldice technique. INTERVENTION: Measurement of intraoperative tension during hernioplasty (low 0-2.0 N, moderate 2.1-4.0 N, high > 4.1 N). MAIN OUTCOME MEASURES: Postoperative pain measured by visual analogue scale (VAS) at rest and activity, pain-related change of ventilatory measurements (8, 24 and 48 hours after intervention), postoperative complications, length of stay in hospital, and recurrence rate at mean 46.7 (range 43-54) months after operation. Data are given as mean (SD). RESULTS: The results for 18 patients were analysed, 2 being lost to follow up. Mean pain score was 17.5 (15.6), 14.8 (15.6) and 12.3 (14.9) at rest 8 hours, 24 hours and 48 hours after operation, during activity 42.0 (16.5), 36.4 (18.5) and 33.7 (19.1) respectively. Most depression of ventilatory measurements was found 8 hours after operation (vital capacity 88.4 (12.5)%. peak flow 81.3 (17.2)%) compared with preoperative values. Complications comprised one seroma, one subcutaneous wound infection, and 3 haematomas. Mean length of stay in hospital was 4.3 (range 2-7) days. At follow up, no recurrences were found. No correlation with intraoperatively-induced tension was found. CONCLUSIONS: Postoperative pain and recurrences depend on many factors, but induced intraoperative tension can be excluded. The reported advantages of tension-free procedures are not based on the avoidance of tension. The Shouldice repair can therefore continued to be used as a routine technique in uncomplicated primary inguinal hernia repair.

Functional and morphologic properties of a modified mesh for inguinal hernia repair.

Inguinal hernia repair is one of the most frequently performed operations. Next to conventional techniques, open and laparoscopic tension-free methods using mesh implants to reinforce the abdominal wall are increasingly carried out, even becoming the standard procedure in many countries. Because of the benefits of material-reduced meshes for incisional hernia repair, a new mesh modification for tension-free inguinal hernia repair has been developed. In the present study this new low-weight mesh (Vypro II) made of polypropylene and polyglactin multifilaments was compared to a common heavy-weight polypropylene mesh (Prolene) regarding their functional consequences and the morphologic tissue response. After implantation in rats as an inlay, abdominal wall mobility was recorded by three-dimensional photogrammetry and the tensile strength of the suture zone and the mesh itself was measured at 3, 21, and 90 days. Explanted tissue samples have been investigated for their histologic reaction in regard to the inflammatory infiltrate, vascularization, and connective and fat tissue ingrowth. Numbers of granulocytes, macrophages, fibroblasts, lymphocytes, and foreign giant body cells have been evaluated to reflect the quality of the tissue response. The cellular response was assessed by measuring DNA strand breaks and apoptosis (TUNEL), proliferation (Ki67), and cell stress (HSP70). The results indicated that restriction of abdominal wall mobility was significantly reduced with Vypro II compared to that seen with heavy-weight mesh modification, and the inflammatory reaction and connective tissue formation were markedly diminished. Apoptosis and cell proliferation showed considerably lowered levels, and expression of cytoprotective HSP70 was significantly increased. The present study thus confirms the benefits of material-reduced mesh modifications. The new low-weight mesh (Vypro II) could be advantageous in inguinal hernia repair.

Review of wound healing with reference to an unrepairable abdominal hernia.

A 58-year-old man has been under our care with an inguinal hernia that has recurred 8 times. This stimulated us to review the biochemistry of wound repair. We studied the composition of his collagen and tried to find out whether it was intrinsically faulty or whether its fault had been caused by the medication he was taken.

Impaired balance of type I and type III procollagen mRNA in cultured fibroblasts of patients with incisional hernia.

BACKGROUND: Recent findings of an impaired protein ratio of type I to type III procollagen showed a disturbed collagen metabolism in incisional hernia development. We analyzed the type I and type III procollagen messenger RNA to investigate whether these findings represent the altered extracellular matrix or a primary defect at the transcriptional level. METHODS: We examined cultured skin fibroblasts of patients with incisional or recurrent incisional hernia in comparison with those without any previous incision (control) and those with a skin scar without clinical appearance of a hernia (scar). Immunohistochemical detection of a lowered protein ratio of type I and type III collagen in the hernia skin tissue leads to mRNA expression analysis. The procollagen mRNA and the ratio of type I to type III procollagen mRNA are detected by reverse transcriptase-polymerase chain reaction and Northern blot analysis, the collagens type I and III by Western blot analysis. RESULTS: Reverse transcriptase-polymerase chain reaction revealed an increase of type I procollagen mRNA in the incisional and recurrent hernia (0.90 +/- 0.04 and 1.19 +/- 0.04, respectively) compared with stable scar (0.54 +/- 0.02) or healthy tissue (0.43 +/- 0.01). The obvious rise of type III procollagen mRNA to 4.13 +/- 0.04 for incisional, 6.02 +/- 0.03 for recurrent hernia, 2.29 +/- 0.04 for stable scar, and 1.72 +/- 0.03 for the healthy tissue showed a significantly decreased ratio of type I to type III procollagen mRNA in the hernia patients as compared with the controls (P <.01). By Western blot analysis, an increase of type I and type III collagen protein and a significant rise in the corresponding ratio in the recurrent hernia group were detected. CONCLUSIONS: The altered synthesis of type I and type III collagen in cultured skin fibroblasts suggests a disorder of collagen metabolism, at least in patients with recurrent hernia. Hence, a basically impaired wound healing process is likely to contribute to the unsatisfactory results of incisional hernia repair.